Oral Cancer News
Compiled by The Oral Cancer Foundation

vitamin C

While alternative health gurus often encourage increasing antioxidants in the diet and the taking of antioxidant nutritional supplements such as beta-carotene, vitamins A, C, and E, and selenium, new research findings suggest that antioxidants could do more harm than good, especially in cancer patients.

The idea is discussed in a perspective article on the promise and perils of antioxidants for cancer patients in the July 10 issue of the New England Journal of Medicine.

Coauthor David Tuveson, MD, PhD, professor and deputy director of the Cold Spring Harbor Laboratory Cancer Center in New York, explained in an interview with Medscape Medical News that the idea that antioxidants could be useful in cancer goes back to Linus Pauling, and is based on observations that oxidation within cells is needed for cell growth. “As cancer cells growth rapidly, a cancer cell would have more oxidation within it than a normal cell,” he added, and the hope was that antioxidants would interfere with these cellular oxidative processes and would suppress the growth.

“Although some early preclinical studies supported this concept,” the authors write, there have now been several clinical trials that have shown no effect of antioxidants on reducing the incidence of cancer, and there have even been suggestions of harm in persons who are at risk for cancer.

Dr. Tuveson noted a clinical trial from Scandinavia in the early 1990s, which found that high doses of antioxidants, particularly beta-carotene, were associated with more lung cancer rather than less as had been hoped for.

There was a similar finding from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), which found that the antioxidants did not reduce the risk for prostate cancer, as had been hoped, and in fact increased the risk in some men.

Dose-dependent Harmful Effect

The perspectives article was prompted by new findings reported earlier this year, he said. An animal study carried out by Swedish researchers showed that the harm from antioxidants was dose-dependent (Sci Transl Med. 2014;6:221ra15). The study was conducted in a genetically engineered mouse model that mimics early human non-small-cell lung cancer. The researchers studied N-acetylcysteine (which is used in patients with chronic obstructive pulmonary disease) and also derivatives of vitamin E, and they found that these antioxidants “actually increased cancer burden and mortality in a dose-dependent manner.”

“The mice got lung cancer faster and they died more quickly of the disease,” Dr. Tuveson said.

In their perspective article, Dr. Tuveson and coauthor Navdeep Chandel, PhD, from Northwestern University in Chicago, address the question of why.

It turns out that all cells have not only oxidative mechanisms producing reactive oxygen species, they also have a mechanism by which they produce antioxidants, and so there is a balance between the 2 in each cell. “And cancer cells, because they make more oxidants, also make more antioxidants,” Dr. Tuveson explained.

“So when adding an antioxidant as a supplement, all you are doing is increasing a pool of what is already there,” he said. “But you are not actually stopping the oxidative mechanisms, and you are not stopping the production of oxidants in the first place, and the pathways that are fuelling cell growth,” he added.

“All you are doing is helping the cancer cell deal with the toxic effects of the oxidants, and by doing so you may be actually making the cancer cell even stronger,” Dr. Tuveson said.

“The antioxidants that we take as a supplement or in our diet don’t go after the root cause of how oxidants promote cancer cell biology,…and our suggestion is that we need to look much more carefully at these mechanisms if we are to truly develop strategies to prevent cancer,” he said.

In their article, the authors propose 2 strategies for further research — the development of antioxidants that target specific intracellular sites of oxidant production, and also a synthetic lethal strategy directed at antioxidants produced within the cell. Both of these strategies are currently at the research stage, with work focused on developing compounds that could be tested in humans.

As for the clinical implications of the research so far, Dr. Tuveson said: “We don’t firmly say that taking antioxidants is dangerous for cancer patients…but I do believe that our article will cause those discussions to begin.”

However, others have already warned cancer patients not to take antioxidants; for instance, prostate cancer patients have been warned against taking selenium, as previously reported by Medscape Medical News.

In addition, there is a question of whether antioxidants may interfere with common cancer treatments, such as chemotherapy and radiotherapy, as these work by increasing oxidation within cancer cells, Dr. Tuveson commented. This is an area that needs to be studied more, he said.

This issue of antioxidants being harmful to cancer patients was raised last year by Nobel laureate James Watson, PhD, who is chancellor emeritus at the Cold Spring Harbor Laboratory. He described a new hypothesis on reactive oxygen species that he considers is “among my most important work since the double helix.”

Dr. Watson proposed that antioxidant levels within cancer cells are a problem and are responsible for resistance to treatment, and that the untreatability of late-stage cancer might be the result of “its possession of too many antioxidants.”

“The time has come to seriously ask whether antioxidant use more likely causes than prevents cancer,” Dr. Watson said. Nutritional intervention trials have shown no obvious effectiveness in preventing cancer or in lengthening mortality, and, “in fact, they seem to slightly shorten the lives of those who take them.”

Dr. Tuveson, who works at the same institution, commented at the end of the interview that “Dr. Watson is usually a few steps ahead of the rest of us.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Nutritionally speaking, good things come in sweet—and tart—little packages. Research is discovering berries pack a nutritional punch due to their vitamin, fiber and antioxidant content.

Botanically speaking, berries are indehiscent fruits (they don’t need to be opened to release their seeds) that ripen through the ovary wall. However, any small, edible fruit with multiple seeds is typically considered a berry.

In addition to lending flavor and brilliant colors to a wide variety of dishes, all berries are packed with an array of antioxidants, nutrients and potential health benefits. Berries that are especially antioxidant-rich include fresh crowberries, bilberries, black currants, wild strawberries, blackberries, blueberries, goji berries, sea buckthorn, blueberries and cranberries. However, the antioxidant content of berries varies based on the geographical growing condition. And, while fresh berries are an excellent source of antioxidants, total phenol content drops during processing. In fact, processed berry jams and syrup contain approximately half the antioxidant capacity of fresh berries, and juices show the greatest loss of anthocyanins and tannins due to the removal of seeds and skin (Nutrition Journal, 2010; 9:3; Journal of Agricultural and Food Chemistry, Jan 13, 2012).

Botanical berries
Shiny, scarlet-colored cranberries are rich in vitamin C, loaded with antioxidants, including flavonoids, and score higher in their ORAC score than many other fruits (“Oxygen Radical Absorbance Capacity (ORAC) of Selected Foods—2007”, USDA ARS). Cranberries are perhaps best known for the role their juice plays in the prevention of urinary tract infections (UTI) in women, particularly those with recurrent UTIs (Cochrane Database Systems Review, 2008; 23:CD001321). However, cranberries may also inhibit the growth and proliferation of some types of cancer cells (Journal of Nutrition, 2007; 137:186S-193S), reduce low-density lipoprotein (LDL) oxidation and platelet aggregation, and improve vascular function (Nutrition Reviews, 2010; 68:168-177; Nutrition Reviews, 2007; 65:490-502). In addition, polyphenols isolated from cranberries appear to inhibit the formation of cariogenic bacteria and reduce both inflammation and the production of enzymes that contribute to the destruction of the extracellular matrix in periodontal disease, making them beneficial for oral health (Journal of the Canadian Dental Association, 2010; 76:a130).

Processing and storage affects the phytochemicals found in cranberries. Anthocyanins are present at much higher levels than flavonols in cranberries, but the reverse is true for cranberry juice, due, in part, to the instability of anthocyanins. Some flavonols are also degraded during processing but to a lesser extent than anthocyanins (Critical Reviews in Food Science and Nutrition, 2009; 49:741-781).

Also leading the nutritional way is the tiny blueberry. According to the U.S. Highbush Blueberry Council, Folsom, CA, blueberries are packed with vitamin C, dietary fiber, potassium and antioxidants, with a total of 6,552 ORAC units per 100 grams. Further, many studies have indicated blueberry supplementation can help mitigate age-related neurodegenerative diseases. In one study, for example, rats fed 18.6 grams of dried blueberry extract per kilogram of diet for eight weeks showed a reversal of age-related deficits in brain and behavioral function (The Journal of Neuroscience, 1999; 19:8,114-8,121). The phytochemicals in blueberries also may help protect against some cancers. A study that identified blueberry anthocyanins also determined their ability to inhibit the growth of colon, breast, oral and, especially, prostate cancer cell lines. The same study showed blueberries were effective in inducing cell death of colon-cancer cells (Journal of Agricultural and Food Chemistry, 2006; 54:9,329-9,339).

Other less commonly consumed berries show promising health benefits. Though relatively few health-related studies have been conducted using black, white and red currants, one study using mixed berries, including currants, found that consumption of two portions of berries daily (including black currant purée on alternating days) resulted in favorable changes in high-density lipoprotein (HDL) cholesterol, blood pressure and platelet functioning (American Journal of Clinical Nutrition, 2008; 87:323-331). Red and black currants are an excellent source of vitamin C, and black currants are also an excellent source of fiber and good source of manganese and potassium.

Wolfberries, otherwise known as goji berries, contain several antioxidants, notably zeaxanthin, one of the two antioxidants found in the retina of the eye. One double-blind, placebo-controlled study in healthy elderly subjects found that, compared to placebo, daily supplementation with goji berry (13.7 grams per day) for 90 days increased plasma zeaxanthin and antioxidant levels while protecting from hypopigmentation and soft drusen accumulation (yellow deposits under the retina) in the macula of the eye (Optometry & Vision Science, 2011; 88:257-262). Additional studies have found that goji berry juice improves antioxidant biomarkers in healthy humans (Nutrition Research, 2009; 29:19-25), subjective feelings of well-being, neurologic and psychologic performance and gastrointestinal functioning (Journal of Alternative and Complementary Medicine, 2008; 14:403-412).

More research needs to be done on the health benefits of gooseberries and muscadine grape berries, but they, too, have a great nutrition profile. Gooseberries are an excellent source of vitamins A and C, and a good source of potassium and fiber. Muscadine grape berries are an excellent source of manganese, a good source of fiber and contain reseveratrol (American Journal of Enology and Viticulture, 1996; 47:57-62).

Non-botanical berries
In addition to the nutrition attributes for botanical berries, non-botanical berries, including strawberries, chokeberries, blackberries and raspberries, are also loaded with nutrients and antioxidants.

Chokeberries (Aronia melanocarpa) contain a mix of many antioxidants, including procyanidins, anthocyanins and phenolic acids. A review of studies to date on chokeberries indicate they may be a promising functional food for diseases related to oxidative stress, but more rigorous scientific research is necessary (Phytotherapy Research, 2010; 24:1,107-1,114).

Raspberries are an excellent source of vitamin C, manganese and dietary fiber, and a good source of vitamin K. However, much of the interest in raspberries stems from their anthocyanin and ellagic acid content. In vitro studies show ellagic acid is protective against cancer (Journal of Nutrition and Biochemistry, 2004; 15:672-678). And this antioxidant, as well as the overall antioxidant capacity of raspberries, is similar in fresh commercial, freshly picked and frozen raspberries (Journal of Agricultural and Food Chemistry, 2002; 50:5,197-5,201).

All berries are full of antioxidants and nutrients. And, the various colors, textures and different forms of berries, including frozen, fresh, dried and pulp, make berries a versatile, nutritious, eye-appealing and tasty addition to a variety of foods and beverages.

About the author:
Marie Spano, M.S., R.D., CSCS, is a nutrition communications expert whose work has appeared in popular press magazines, e-zines and nutrition-industry trade publications. She has been an expert guest on NBC, ABC and CBS affiliates on the East Coast.

Numerous studies suggest that avoiding excess weight, exercising regularly, and eating a diet heavy on fruits and vegetables decreases the risk of many diseases, including cancer. But as the expanding obesity epidemic has shown, there are major obstacles to getting broad swaths of people to adopt such a healthful lifestyle. So, for many years, cancer researchers have investigated whether specific nutrients—those that epidemiologic and animal model studies have suggested could sway cancer’s course—could decrease cancer risk.

Much has been learned from this work, researchers in the field say, but, as is the case with treatment, each new discovery points to new areas of focus and other potential avenues of progress.

With promising bioactive compounds in the pipeline, many prevention researchers are focused on figuring out not just whether something like sulforaphane, a natural compound found in broccoli and broccoli sprouts, can kill cancer cells in a test tube or animal model—which it does, quite well—but how, at the molecular level, it accomplishes this task, whether there are some cancer cells that are more likely to respond to it, and whether there are ways of discerning early on that the intervention is having its intended effect.

Prevention: A Complex Matter

A number of supplements have been tested in large prevention trials, including vitamins A, C, and E; selenium; beta-carotene; and folic acid. At least one trial has demonstrated a reduction in cancer deaths with a combination of supplements, while several others found no reduction or even a small increased risk.

“There was suggestive evidence in humans” to support the large clinical trials conducted to date, said Dr. Peter Greenwald, director of NCI’s Division of Cancer Prevention (DCP). Millions of people are taking supplements in the belief that they can improve their health, including preventing cancer, he continued, so getting data from randomized clinical trials—the gold standard of biomedical research—is critical.

But given the complexity of cancer, acknowledged Dr. Alan Kristal, a long-time cancer prevention researcher at the Fred Hutchinson Cancer Research Center, it raises questions about whether “high doses of micronutrients are going to have an impact on cancer risk.”

And Dr. John Milner, chief of DCP’s Nutritional Science Research Group, says that, in the pursuit of nutrition-based cancer prevention, it’s more than just the complexity of cancer that has been underestimated. “In many ways, the lesson is that food and what we need to live is a lot more complex than we’ve ever thought,” Dr. Milner said.

It’s that complexity that researchers are increasingly tackling more directly.

Small Steps

At Ohio State University, Dr. Gary Stoner and his colleagues have been studying the cancer prevention potential of black raspberries for the last decade. Much of their work has focused on a powdered form of the entire berry, which eliminates the water that makes up 85 to 90 percent of the berry’s weight.

The researchers began with laboratory and animal model studies, and when these studies demonstrated that the berry powder had prevention potential, they transitioned to small human trials. Some promising results have been seen in early stage human trials for esophageal, oral, and colorectal cancer prevention. A small skin cancer prevention trial is on the immediate horizon.

In the case of oral cancer, the Ohio State team worked with collaborators from the University of Kentucky to produce a berry powder-infused gel that is applied to precancerous oral lesions. Treatment for 6 weeks shrunk the lesions by as much as 50 percent and decreased the activity of genes related to cell growth and proliferation. Based on the results, NCI is funding a phase II, placebo-controlled trial of the gel.

“You can establish that something might work in a much smaller trial with a lot less money,” Dr. Stoner said. “You can get a good idea if it will inhibit proliferation in a trial of 20 patients.”

Small human trials, explained Dr. Kristal, can “integrate what’s known about the carcinogenesis process and see whether we can manipulate that process with micronutrients or bioactive compounds.” Even then, he stressed, they have to be carefully designed to ensure that they produce meaningful results that can potentially inform further studies and larger trials.

At UCLA’s Jonsson Comprehensive Cancer Center, for instance, Dr. William Aronson is leading a phase II clinical trial of fish oil supplements, which are a plentiful source of omega-3 polyunsaturated fatty acids. The trial is randomly assigning men with prostate cancer who are scheduled to have their prostates removed to a low-fat diet with fish oil supplements or a standard Western diet for 4 to 8 weeks.

By analyzing tissue and blood samples taken before and after surgery, the researchers aim to determine whether the low-fat diet and fish oil combination alters the levels of certain serum and tissue proteins that may be associated with prostate cancer progression. “Such biomarkers may indicate that the intervention is working and will be an essential component of long-term human dietary intervention trials,” Dr. Aronson explained.

Even here there are challenges, noted Dr. Kristal, because once potential biomarkers are discovered, it then has to be demonstrated that a change in a biomarker alters the course of the disease.

Both short-term trials and analyses of tissue samples from the large trials that have already been conducted may also help to address another critical issue: variability in response. “Any time you do a study, even with drugs, you don’t get 100 percent effectiveness. You only get some people who respond,” said Dr. Milner. “That’s what happens with many nutrients as well.”

All of this work, stressed Dr. Greenwald, is moving in the right direction to get these nutritional interventions into phase II and III trials. “If you have studies that clearly show an effect on biological endpoints that we think are related to cancer risk, a mechanism, and human data, that’s very useful information,” he said.

Moving Forward to Phase III Trials

While more early stage trials are on the horizon, those in the field agree that there will probably be somewhat fewer large phase III trials. One such trial, the VITamin D and omegA-3 triaL, dubbed VITAL, is set to begin enrolling the first of 20,000 planned participants in January 2010. The NCI-supported trial will test whether regular use of vitamin D and fish oil supplements, taken either alone or in combination, reduces overall cancer risk (as well as the risk of heart disease and stroke) in women aged 65 and older and men aged 60 and older.

“There is a narrow window of opportunity for doing a trial of this nature,” said the study’s principal investigator, Dr. JoAnn Manson, from Brigham and Women’s Hospital and Harvard Medical School. Only in the last 2 years, Dr. Manson believes, “has the strength of the evidence for vitamin D and fish oil reached that threshold” to support launching a trial of this size. In addition, she argued, if researchers wait too long, “so many people could be taking [these supplements] that the trial will no longer be feasible.”

Sales data on supplements support her concern. According to The Nielsen Company, sales of vitamins and supplements for June 2008 to June 2009 were up 5 percent over the previous year, totaling $1.5 billion. Vitamin D and fish oil are two of the biggest sellers.

VITAL researchers will analyze blood samples from a subset of participants to see if baseline levels of markers like 25-hydroxy vitamin D, the primary form of vitamin D circulating in the blood, and omega-3s correlate with reduced disease risk. And because the trial has a specific focus on recruiting a large number of minority participants, the researchers can analyze whether factors like participants’ race or ethnic background influenced the response to the supplements and whether supplement consumption can reduce health disparities by race.

Advances may not come as fast as some might like, but they are happening, said Dr. Aronson. “I think we’re going to make very significant progress over the next 5 years and we’re going to gain important information that we can incorporate into larger trials.”

60 percent seek natural ‘cures’ despite warnings from doctorsTAMPA, Fla. – With much of her lower body consumed by cancer, Leslee Flasch finally faced the truth: The herbal supplements and special diet were not working.

“I want this thing cut out from me. I want it out,” she told her family.

But it was too late. Her rectal cancer — potentially curable earlier on — had invaded bones, tissue, muscle, skin. The 53-year-old Florida woman could barely sit, and constantly bled and soiled herself.

“It was terrible,” one doctor said. “The pain must have been excruciating.”

Flasch had sought a natural cure. Instead, a deadly disease ran its natural course. And the herb peddlers who sold her hope in a bottle?

“Whatever money she had left in life, they got most of it,” said a sister, Sharon Flasch. “They prey on the sick public with the belief that this stuff can help them, whether they can or can’t.”

Some people who try unproven remedies risk only money. But people with cancer can lose their only chance of beating the disease by skipping conventional treatment or by mixing in other therapies. Even harmless-sounding vitamins and “natural” supplements can interfere with cancer medicines or affect hormones that help cancer grow.

Preying on insecuritiesYet they are extremely popular with cancer patients, who crave control over their disease and want to do everything they can to be healthy — emotional needs that make them vulnerable to deceptive claims. Studies estimate that 60 percent of cancer patients try unconventional remedies and about 40 percent take vitamin or dietary supplements, which do not have to be proved safe or effective and are not approved by the federal Food and Drug Administration.

None has turned out to be a cure, although some show promise for easing symptoms. Touch therapies, mind-body approaches and acupuncture may reduce stress and relieve pain, nausea, dry mouth and possibly hot flashes, and are recommended by many top cancer experts. A recent study found that ginger capsules eased nausea if started days before chemotherapy.

Many hospitals offer aromatherapy, massage, meditation, yoga and acupuncture because patients want them and there is little risk of physical harm. They call this complementary or integrative medicine because it is in addition to — not in place of — conventional treatments.

At the other end of the spectrum are quacks selling fringe therapies and supplements through testimonials, not proof. Laetrile, “detoxifying” coffee enemas, shark cartilage — the miracle cures change but the bogus claims remain the same.

“What I am noticing in the last year or two is a resurgence of these things. It’s coming back,” said Barrie Cassileth, integrative medicine chief at Memorial Sloan-Kettering Cancer Center in New York and a longtime adviser to the American Cancer Society.

The Internet fuels this trend by letting people buy direct and bypass doctors who could help them see through scams and misleading claims of scientific proof. Sadly, some Web sites are run by quacks — a “doctor” title doesn’t mean the remedy is safe or effective.

“A lot of these doctors prey on people’s insecurities and need for hope,” said Dr. Roy Herbst, lung cancer chief at the University of Texas M.D. Anderson Cancer Center.

About 7 percent of cancer patients go straight to an alternative approach, sometimes traveling to Mexico, the Bahamas or a “spa” in Europe for treatments not allowed in the United States, Cassileth’s research found. Most cancers spread slowly, so people can be temporarily fooled into thinking herbs or special diets are keeping it at bay.

“After they’ve been there some months they’ll realize things are not working. But with cancer, you get one chance. By the time they get back to a reasonable hospital, they’re dead. Nothing can be done for them,” she said.

Ways that supplements and fringe therapies can harm:

Financially. Pills that seem cheap actually cost a lot if they are worthless or are bought in place of real medicine, fresh fruits and vegetables, or other things known to boost health.

Medically. Trying an alternative remedy can delay the time until a patient receives an effective treatment, allowing the cancer to spread. A potentially curable cancer may become untreatable — as Leslee Flasch found out when she belatedly sought the surgery that had been recommended. Having such an advanced cancer without standard medical care must have caused excruciating pain, said one of her physicians, Dr. Lodovico Balducci at Moffitt Cancer Center in Tampa.

Physically. Supplements, even those claimed to be natural, have biological effects and can interact dangerously with a wide array of medicines.

Psychologically. Futile treatment raises false hope and deprives people of the chance to prepare for the end of life and die in dignity and comfort.

Leslee Flasch believed that dietary supplements would make her stronger and help fight the cancer — a belief her other surviving sister, Donna Flasch, still shares despite Leslee’s death.

But getting nutrients from pills is different than getting them from a balanced diet, nutrition experts say.

“So many people think, ‘Well, if a little bit is good, then more is better,’ and that’s definitely not true with most dietary supplements,” said Kathy Allen, a Moffitt Cancer Center dietitian.

Examples of potential harm:

Vitamin E can prolong bleeding time and has forced cancellation or delay of cancer surgeries; some studies suggest it may raise the risk of certain cancers.

Folic acid supplements may raise the risk for precancerous growths in the colon.

Vitamin C in large doses may help cancer cells resist chemo and radiation

Herbals and dietary supplements can undermine cancer treatments in ways that patients can’t feel and doctors can’t measure. When a treatment fails, it’s impossible to say whether it was due to the person’s cancer or because a supplement subtly interfered.

“We know that there’s some harm going on. We just don’t know the magnitude of it,” said Dr. Jeffrey White, the National Cancer Institute’s complementary and alternative medicine chief.

Unaware of dangers
Studies show that as many as two-thirds of cancer patients who use unproven remedies do not tell their doctors. Sometimes it is because they fear disapproval, but often they do not realize this can harm their care.

“I didn’t think they were medications. They’re not prescription, they’re not drugs. This is all natural substances,” said Vince Palella, a Bradenton, Fla., prostate cancer patient.

A Moffitt dietitian, Diane Riccardi, discovered that Palella was taking dozens of pills a day, including a saw palmetto extract. That supplement might have interfered with his hormonal cancer treatments or the monitoring to see if the those treatments were working.

“There’s absolutely no way of knowing” if it did, Riccardi said.

Another supplement that can pose a risk for prostate cancer patients is DHEA, which can affect testosterone levels, said Phyllis Matthews, a urology nurse practitioner at a group of Veterans Affairs clinics in the Denver area.

Cancer doctors also worry about isoflavones and other soy-related supplements; some research suggests they might stimulate breast tissue. Breast cancer patients on tamoxifen or aromatase inhibitors like Femara or Arimidex should not use red clover, dong quai or licorice because of estrogen-stimulating components, say guidelines from the Society for Integrative Oncology.

In June, the FDA sent 25 warning letters to sellers of teas, pills and other products sold on the Internet that falsely claim to cure, treat or prevent cancer. They included bloodroot, shark cartilage, coral calcium, cesium, ellagic acid, cat’s claw, Essiac tea and various mushrooms.

In September, the Federal Trade Commission charged five companies with making false and misleading claims for cancer cures and reached settlements with six others. The agency also started a bogus cures Web site to help consumers. A statement explained its reasoning:

Background:
Observational studies suggested that a diet high in fruits and vegetables, both of which are rich with antioxidants, may prevent cancer development. However, findings from randomized trials of the association between antioxidant use and cancer risk have been mostly negative.

Methods:
From 8171 women who were randomly assigned in the Women’s Antioxidant Cardiovascular Study, a double-blind, placebo-controlled 2 x 2 x 2 factorial trial of vitamin C (500 mg of ascorbic acid daily), natural-source vitamin E (600 IU of {alpha}-tocopherol every other day), and beta carotene (50 mg every other day), 7627 women who were free of cancer before random assignment were selected for this study. Diagnoses and deaths from cancer at a specific site were confirmed by use of hospital reports and the National Death Index. Cox proportional hazards regression models were used to assess hazard ratios (represented as relative risks [RRs]) of common cancers associated with use of antioxidants, either individually or in combination. Subgroup analyses were conducted to determine if duration of use modified the association of supplement use with cancer risk. All statistical tests were two-sided.

Results:
During an average 9.4 years of treatment, 624 women developed incident invasive cancer and 176 women died from cancer. There were no statistically significant effects of use of any antioxidant on total cancer incidence. Compared with the placebo group, the RRs were 1.11 (95% confidence interval [CI] = 0.95 to 1.30) in the vitamin C group, 0.93 (95% CI = 0.79 to 1.09) in the vitamin E group, and 1.00 (95% CI = 0.85 to 1.17) in the beta carotene group. Similarly, no effects of these antioxidants were observed on cancer mortality. Compared with the placebo group, the RRs were 1.28 (95% CI = 0.95 to 1.73) in the vitamin C group, 0.87 (95% CI = 0.65 to 1.17) in the vitamin E group, and 0.84 (95% CI = 0.62 to 1.13) in the beta carotene group. Duration and combined use of the three antioxidants also had no effect on cancer incidence and cancer death.

Conclusions:
Supplementation with vitamin C, vitamin E, or beta carotene offers no overall benefits in the primary prevention of total cancer incidence or cancer mortality.

Many people gobble big doses of vitamin C in hopes of boosting their immune system and warding off illness. But new research shows that in people with cancer, the vitamin may do more harm than good.

Researchers at Memorial Sloan-Kettering Cancer Center in New York studied the effects of vitamin C on cancer cells. As it turns out, the vitamin seems to protect not just healthy cells, but cancer cells, too. The findings were published today in the journal Cancer Research.

“The use of vitamin C supplements could have the potential to reduce the ability of patients to respond to therapy,” said Dr. Mark Heaney, an associate attending physician at the cancer center.

Dr. Heaney and his colleagues tested five different chemotherapy drugs on cancer cells in the laboratory. Some of the cells were first treated with vitamin C. In every case, including a test of the powerful new cancer drug Gleevec, chemotherapy did not work as well if cells had been exposed to vitamin C. The chemotherapy agents killed 30 to 70 percent fewer cancer cells when the cells were treated with the vitamin.

A second set of experiments implanted cancer cells in mice. They found that the tumors grew more rapidly in mice that were given cancer cells pretreated with vitamin C.

The researchers found that just like healthy cells, cancer cells also benefit from vitamin C. The vitamin appeared to repair a cancer cell’s damaged mitochondria, the energy center of cells. When the mitochondria is injured, it sends signals that force the cell to die, but vitamin C interrupts that process.

Dr. Heaney measured the buildup of vitamin C levels in cells and said that the levels of vitamin C used in the experiments were similar to those that would result if a patient took large doses of the vitamin in supplement form. Earlier research at the cancer center showed that vitamin C seems to accumulate within cancer cells more than in normal cells.

Patients should eat a healthy diet that includes foods rich in vitamin C, Dr. Heaney said, but it’s the large doses of vitamin C in tablet form that are worrisome.